Document Detail

Requirement for diacylglycerol and protein kinase C in HeLa cell-substratum adhesion and their feedback amplification of arachidonic acid production for optimum cell spreading.
MedLine Citation:
PMID:  8485318     Owner:  NLM     Status:  MEDLINE    
Release of arachidonic acid (AA) and subsequent formation of a lipoxygenase (LOX) metabolite(s) is an obligatory signal to induce spreading of HeLa cells on a gelatin substratum (Chun and Jacobson, 1992). This study characterizes signaling pathways that follow the LOX metabolite(s) formation. Levels of diacylglycerol (DG) increase upon attachment and before cell spreading on a gelatin substratum. DG production and cell spreading are insignificant when phospholipase A2 (PLA2) or LOX is blocked. In contrast, when cells in suspension where PLA2 activity is not stimulated are treated with exogenous AA, DG production is turned on, and inhibition of LOX turns it off. This indicates that the formation of a LOX metabolite(s) from AA released during cell attachment induces the production of DG. Consistent with the DG production is the activation of protein kinase C (PKC) which, as with AA and DG, occurs upon attachment and before cell spreading. Inhibition of AA release and subsequent DG production blocks both PKC activation and cell spreading. Cell spreading is also blocked by the inhibition of PKC with calphostin C or sphingosine. The inhibition of cell spreading induced by blocking AA release is reversed by the direct activation of PKC with phorbol ester. However, the inhibition of cell spreading induced by PKC inhibition is not reversed by exogenously applied AA. In addition, inhibition of PKC does not block AA release and DG production. The data indicate that there is a sequence of events triggered by HeLa cell attachment to a gelatin substratum that leads to the initiation of cell spreading: AA release, a LOX metabolite(s) formation, DG production, and PKC activation. The data also provide evidence indicating that HeLa cell spreading is a cyclic feedback amplification process centered on the production of AA, which is the first messenger produced in the sequence of messengers initiating cell spreading. Both DG and PKC activity that are increased during HeLa cell attachment to a gelatin substratum appear to be involved. DG not only activates PKC, which is essential for cell spreading, but is also hydrolyzed to AA. PKC, which is initially activated as consequence of AA production, also increases more AA production by activating PLA2.
J S Chun; B S Jacobson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular biology of the cell     Volume:  4     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  1993 Mar 
Date Detail:
Created Date:  1993-06-04     Completed Date:  1993-06-04     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  271-81     Citation Subset:  IM    
Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst 01003.
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MeSH Terms
Arachidonic Acid / biosynthesis*,  secretion
Cell Adhesion / physiology*
Diglycerides / metabolism*
Enzyme Activation
Hela Cells
Lipoxygenase / metabolism
Phospholipases A / metabolism
Phospholipases A2
Protein Kinase C / antagonists & inhibitors,  metabolism*
Grant Support
Reg. No./Substance:
0/Diglycerides; 506-32-1/Arachidonic Acid; EC; EC Kinase C; EC 3.1.1.-/Phospholipases A; EC A2

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